Brachytherapy in situ dose-painting administered via gold-nanoparticle eluters

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DESCRIPTION (provided by applicant): The candidate has demonstrated great potential to successfully transition into independence as evinced by his research productivity, high quality of research publications, awards, and honors. His immediate career goal is to develop the new BANDAGE for prostate cancer treatment approach and successfully transition into independence. His long term goal is to develop an internationally recognized research program in applications of nanotechnology in radiation therapy. The KO1 award will provide protected time for carrying out the proposed research and complementary didactic and clinical training components Environment: The institutional environment, Dana-Farber Cancer Institute (DFCI), Harvard Medical School is optimally suitable for conducting the proposed research and career development of the candidate. The necessary didactic, clinical and research resources are available together with key faculty to work with. Research: The overall goal of the proposed research is to develop a new brachytherapy application with in situ dose-painting administered via gold-nanoparticle eluters (BANDAGE) that would circumvent current critical barriers to salvage radiotherapy and radiation boosting for prostate cancer. BANDAGE seeks to circumvent these critical limitations by loading routinely used brachytherapy spacers with radio-sensitizing (but) biocompatible gold nanoparticles (AuNP), which can be released/eluted in situ after implantation in prostate tumors. The AuNP release, in situ, from the spacers and consequent 3-dimensional intra-tumor bio-distribution over time may be customized e.g. by varying AuNP size, spacer position, concentration, and other parameters to provide sub-volume AuNP-aided radiation boosting of the prostate without increased toxicity to healthy tissue. The central hypothesis of this K01 application is that the new BANDAGE for prostate cancer treatment modality is a more efficacious approach for salvage radiotherapy and radiation boosting, because of the potential for customizable sub-volume boosting without increase in normal tissue toxicity. The specific aims are: 1) Establish customizable intra-tumor biodistribution profiles and pharmacokinetics of gold nanoparticles (AuNP) released from gold-loaded brachytherapy spacers in pre-clinical models; 2) Demonstrate significant therapeutic enhancement using BANDAGE in preclinical models; 3) Develop treatment planning software tools for BANDAGE for prostate cancer. Relevant to the mission of the NCI, the expected outcomes of this project include: development of potentially improved treatment option (BANDAGE) for prostate cancer patients, and career development of the applicant into a successful and productive independent investigator in the fight against cancer.